Direct functionalization of arenes by primary alcohol sulfonate esters catalyzed by gold(III)

Article abstract of DOI:10.1021/ja046890q

Alkylation of arenes by primary alcohol triflate or methanesulfonate esters can be efficiently catalyzed by AuCl₃ with silver triflate. Copyright

Full text of DOI:10.1021/ja046890q

Published on Web 10/01/2004
Direct Functionalization of Arenes by Primary Alcohol Sulfonate Esters
Catalyzed by Gold(III)
Zhangjie Shi and Chuan He*
Department of Chemistry, The UniVersity of Chicago, 5735 S. Ellis AVenue, Chicago, Illinois 60637
Received May 26, 2004; E-mail: chuanhe@uchicago.edu
Table 1. Functionalization of Arenes with Primary Sulfonate
Organic transformations catalyzed by gold have been a focus of
attention recently.1 Gold(I) and gold(III) show unique activity in
mediating reactions involving alkynes. In contrast, gold-catalyzed
arene functionalization has been less developed. Such processes
could provide efficient ways to construct C-C bonds from simple
arene substrates. We and others have recently reported function-
alization of arenes with gold.1b,1h,1j,2a Our group also discovered a
gold-catalyzed alkylation of arenes by epoxides.2b We report here
a unique reaction for functionalizing arenes with primary alcohol
triflate or methanesulfonate esters and studies revealing mechanistic
aspects of the reaction.
Estersa
Alkylation of aromatic groups is typically achieved with Friedel-
Crafts reactions.3 Most of these reactions are run under harsh
conditions with either high concentrations of acids or large amounts
of strong Lewis acids, which can hardly be tolerated by many
functional groups. Thus, direct functionalization of aromatic C-H
under mild conditions holds great promise in synthetic chemistry.4
Encouraged by our recent success with gold(III)-catalyzed arene
functionalization,2 we explored reactions between arenes and
primary alcohol triflate and methanesulfonate esters. Such reactions
could give linear products with the primary carbon linked to the
arene (eq 1). We found that a reaction between 0.5 mmol of
pentamethylbenzene and 1.0 mmol of n-butyl triflate catalyzed by
5 mol % AuCl3/3AgOTf at 120 °C in dicholoethane gave a linear
product in 72% isolated yield (Table 1, entry 1). No other side
product was observed from the reaction. The presence of both gold
and silver is required for the reaction.
With a chloro-substituted triflate ester, the linear product could
still be obtained with the chloride group intact in a reasonable yield
(Table 1, entry 6). This result shows the potential functional group
tolerance of the reaction. Primary alcohol methanesulfonates could
also be employed as the substrate. For instance, 2-phenethyl meth-
anesulfonate, despite the presence of a benzylic carbon, reacted with
pentamethylbenzene to give the linear product (Table 1, entry 7).
To our surprise, when mesitylene was employed as the arene
substrate, approximately equal amounts of linear and branched pro-
ducts were generated (Table 1, entry 3). When p-xylene was tested,
more branched product was observed. The branched product was
produced predominantly with benzene (Table 1), but ∼5 mol % of
the linear product was also observed. It appears that there are two
mechanisms operating here. For electron-rich arenes, a gold(III)-
mediated reaction, which seems to go through an SN2 type mech-
anism, gives linear products. With benzene or other less-electron-
rich arenes, a Friedel-Crafts pathway may take place to give the
branched products. This second pathway could be catalyzed by
metal ions and/or the acid generated from the auration reaction. A
control reaction was run between 1.0 mmol of pentamethylbenzene
and 2.0 mmol of n-butyl triflate in the presence of 0.15 mmol of
triflic acid. The branched product (30%) together with ∼50% pen-
tamethylbenzene was observed after 2 days. The exact mechanism
that leads to the branched products needs further investigation.
a All reactions were conducted at 120 °C in ClCH2CH2Cl with 0.5 mmol
of arene, 1 mmol of sulfonate ester, and 5 mol % AuCl3/3Ag(OTf) for 48
h (entries 1 and 7 need only 20 h). b Yields were determined by GC; isolated
yields are also shown for entries 1, 6, and 7 in parentheses. c An additional
product (∼20%) with two linear alkyl groups attached to the arene was
also observed. d No second product was observed. e 10 mol % catalyst and
4 equiv of the ester were used. f Ms stands for methanesulfonate.
To study the mechanism, we prepared a dichlorophenylgold-
(III) complex5 and treated it with 2 equiv of AgOTf and 2 equiv of
n-butyl triflate; 30% of the linear product was obtained after 2 days.
The yield of the linear product increased to 70% after 7 days of
reaction.6 Importantly, branched product was not obserVed during
this reaction. The phenylgold(III) species, once formed, does lead
to the linear product upon reacting with n-butyl triflate, but in a
slow rate.
To further probe the reaction mechanism, we ran the reaction
between pentamethylbenzene and n-butyl triflate with 20 mol %
catalyst for 1 h. The reaction was stopped by adding saturated
aqueous NaCl solution. Approximately 65% of the starting material
was observed together with ∼12% of the linear product 1 on the
basis of gas chromatography/mass spectrometry (GC/MS) analysis
(Scheme 1 and Supporting Information Figure S2). Importantly,
∼20% of the chloro-substituted pentamethylbenzene (2) was also
observed. This product comes from the arylgold(III) species upon
treatment with aqueous NaCl solution, as implicated from previous
studies.5 We also confirmed that treating isolated arylgold(III)
complexes with saturated aqueous NaCl solution gave high yields
of the chloro-substituted arenes. Thus, the results indicate that
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J. AM. CHEM. SOC. 2004, 126, 13596-13597
10.1021/ja046890q CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
be noted that the reaction is sensitive to steric hindrance. For in-
stance, with a secondary methanesulfonate ester (Table 2, entry 3),
the product was obtained in a very poor yield under the same reac-
tion conditions. This result further argues against a pure Lewis acid
mechanism. Previously, it was shown that scandium(III) triflate can
catalyze the alkylation of aromatic compounds with methanesulfon-
ates derived from secondary alcohols through a Friedel-Crafts
process, which is quite different from the reaction described here.8
In summary, we report a gold(III)-catalyzed functionalization
of aromatic C-H with primary alcohol triflate or methanesulfonate
esters to construct C-C bonds. Linear substituted arene products
were prepared. We also showed that chromans and benzopyranones
can be synthesized in good yields with the use of this method.
Mechanistic studies indicate the involvement of the arylgold(III)
species as the reaction intermediate. This intermediate then reacts
with the sulfonate ester to give the final product.
almost all gold(III) is in the arylgold(III) form during the course
of the reaction.
The method described here can be used to construct cyclic struc-
tures, as shown in Table 2. Various chromans can be prepared in
good to excellent yields. Benzopyranones can also be obtained in
good yields from the substrates shown in entries 11-14 (Table 2).
The ester bond in the product can be hydrolyzed (eq 2), and this
provides a good method for accessing a group of important stru-
ctures7 with modification at the ortho-position of phenols. It should
Acknowledgment. This research was supported by the Uni-
versity of Chicago and an award from Research Corporation
(RI1179). Acknowledgment is made also to the Donors of the
American Chemical Society Petroleum Research Fund (PRF 38848-
G3) for support of this research.
Table 2. Gold-Catalyzed Intramolecular Cyclialkylationa
Supporting Information Available: Experimental details and
Supporting Information Figures S1 and S2. This material is available
free of charge via the Internet at http://pubs.acs.org.
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